Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.

person Ce Cheng The University of Arizona Cancer Center, Tucson, AZ info_outline Ce Cheng, Iloabueke Gabriel Chineke, Ali McBride, Juan Chipollini, Edward Paul Gelmann, Alejandro Recio-Boiles

Authors person Ce Cheng The University of Arizona Cancer Center, Tucson, AZ info_outline Ce Cheng, Iloabueke Gabriel Chineke, Ali McBride, Juan Chipollini, Edward Paul Gelmann, Alejandro Recio-Boiles Organizations The University of Arizona Cancer Center, Tucson, AZ, The University of Arizona Cancer Center, Arizona, AZ, University of Arizona Cancer Center, Tucson, AZ Abstract Disclosures Research Funding No funding received None Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I 2 = 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I 2 = 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I 2 = 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I 2 = 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I 2 = 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I 2 = 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I 2 = 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I 2 = 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I 2 = 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I 2 = 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I 2 = 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.